79 The International Mesothelioma Interest Group (IMIG) has released updated guidelines aimed at improving the pathologic diagnosis of mesothelioma, an uncommon yet serious tumour often linked to asbestos exposure. Published in the Archives of Pathology & Laboratory Medicine, these guidelines seek to provide practical advice for pathologists worldwide, ensuring more accurate diagnosis and better patient outcomes. Mesothelioma, which primarily affects the pleura and peritoneum, remains challenging to diagnose due to its varied presentation and similarities with other malignancies. The IMIG’s revised guidelines offer comprehensive recommendations based on the latest scientific evidence and expert consensus. Due to its rarity and morphological overlap with other tumours, mesothelioma diagnosis can be challenging. The primary goal of the updated guidelines is to standardise the diagnostic approach across different institutions and pathologists, ensuring consistency and accuracy. The guidelines cover a range of diagnostic techniques, including histomorphologic evaluation, immunohistochemical staining, and molecular assays. The guidelines emphasise the importance of histomorphologic evaluation in diagnosing mesothelioma. Pathologists are advised to differentiate between the three main subtypes of mesothelioma: epithelioid, biphasic, and sarcomatoid. Recognising morphological variants and patterns, as well as common pitfalls, is crucial for accurate diagnosis. For example, epithelioid mesothelioma usually has a tubulopapillary or trabecular structure, while sarcomatoid mesothelioma has spindle cells that look like fibrosarcoma. Immunohistochemistry plays a pivotal role in confirming mesothelial lineage and distinguishing mesothelioma from other malignancies. The guidelines recommend using a panel of mesothelial and epithelial markers. Some markers for mesothelial cells are calretinin, WT1, and cytokeratin 5/6. Markers for epithelial cells, like MOC-31 and Ber-EP4, help rule out adenocarcinomas. Novel markers like Merlin and p53 are also highlighted for their diagnostic value. Molecular studies are increasingly important in the diagnosis of mesothelioma. The guidelines discuss the utility of fluorescence in situ hybridisation (FISH) for detecting CDKN2A deletions, as well as next-generation sequencing panels. These assays can identify genetic alterations characteristic of mesothelioma, such as BAP1 mutations, which are prevalent in epithelioid mesotheliomas . The guidelines offer detailed recommendations for the routine reporting of mesothelioma, including grading epithelioid mesothelioma and assessing prognostic parameters. A two-tiered grading system based on mitotic activity and nuclear atypia is recommended to facilitate clinical decision-making. High-grade tumours, characterised by severe nuclear atypia and high mitotic rates, are associated with a poorer prognosis. Mesothelioma in situ (MIS), the non-invasive precursor to diffuse mesothelioma, is addressed in the guidelines. For MIS to be diagnosed, BAP1 loss or CDKN2A deletion must be shown without showing invasive tumour growth. This diagnosis is particularly challenging due to the subtle histologic features and the need for advanced molecular testing. The role of cytology in diagnosing mesothelioma is also covered. While cytologic samples from effusions can be diagnostic, they do not allow for the assessment of stromal invasion. Therefore, integrating immunohistochemical and molecular studies is essential for accurate cytologic diagnosis. The guidelines recommend using large biopsy specimens obtained through thoracoscopy or laparoscopy to complement cytologic findings. The guidelines also have a section on peritoneal mesothelial lesions that are not cancerous, like peritoneal inclusion cysts and well-differentiated papillary mesothelial tumours. These lesions can mimic malignant mesothelioma, making accurate diagnosis critical. Immunohistochemical staining for BAP1 and MTAP helps differentiate these benign lesions from their malignant counterparts.